Our objective is to investigate the role of the brain in the mechanism of initiation of cardiac arrhythmias, particularly ventricular fibrillation (VF). We have shown that cardiac responses and arrhythmias can be influenced by several experimentally defined states of the central nervous system including: (1) psychological stress evoked by unfamiliar surroundings, (2) slow wave and rapid eye movement sleep stages, (3) tone-shock cardiac conditioning, (4) electric brain stimulation, and (5) functional brain blockade in a particular cerebral system. Our electrophysiological studies have suggested a specific brain system, involving the frontal lobe, mediates the effects of psychological stress on the myocardium. Local cryogenic blockade in this system appears from our preliminary results to prevent the initiation of VF in the ischemic heart. The implication of this result is, if pharmacologic intervention could be achieved to duplicate the effect of the cryogenic blockade, then sudden death could be prevented in the animal or human who has an ischemic myocardium. Currently we are using a new method (developed by us) of freeze-fixation in the brain of a conscious animal to investigate the neurochemical transactions that occur during psychologic and physical stress. A second of our interdisciplinary approaches to the problem of sudden death is to understand how the deleterious brain states affect the heart. The correlated measures we are proposing to make under the various cerebral conditions will each be obtained in several small areas of the left ventricle of the closed-chest conscious pig and they are: refractory interval to intramural and epicardial electric stimuli, metabolic state of the tissue (glycogen breakdown, phosphorylase a/b ratio, cyclic AMP level), rate of contraction (Doppler-shift in ultrasonic waves) and arterial blood flow (pulsed Doppler-shift determination of blood velocity). Such measures should enable us to determine the regional myocardial correlates of the dispersion of refractorines that is thought to underlie arrhythmiagenesis by reentry.